Conventionally, there has been known a production process of an optically active 2-alkylcysteine, in which an optically active cysteine methyl ester as a starting material is cyclized with pivalaldehyde and protected with formaldehyde, and then methylated with a lithium reagent and methyl iodide, followed by ring-opening with hydrochloric acid and deprotection so as to obtain an optically active 2-methylcysteine in the form of hydrochloride (see Patent Document 1 and Non-Patent Document 1, for example). The obtained optically active 2-methylcysteine can be esterified by addition of acetyl chloride thereto in alcohol. However, this process requires the optically active substance to be a starting material that is expensive. In addition, this process requires a large number of complicated steps, and also requires expensive reagents. Thus, it is hardly said that this is an industrially excellent process.
Further, there has been reported another process of producing an optically active 2-alkylcysteine in which an L-cysteine ethyl ester as a starting material is cyclized with a nitrile compound and methylated with a methylating agent such as methyl iodide to obtain a 4-alkylthiazoline-4-carboxylic acid ester, and the obtained ester is converted to a racemic body of a 4-methylthiazoline-4-carboxylic acid by a basic hydrolysis and then subjected to optical resolution using a basic optical resolution agent such as phenethylamine, or the 4-alkylthiazoline-4-carboxylic acid ester is subjected to a stereoselective hydrolysis using microorganisms to perform optical resolution and then hydrolyzed, to yield an optically active 2-methylcysteine (see Patent Documents 2 and 3, for example). Although this process uses an optically active substance as a raw material, it yields an intermediate of racemic body during the reaction, and requires the optical resolution to be carried out again. Hence, this process includes complicated steps, and it is hardly said that this is an industrially excellent process.
Meanwhile, it is anticipated that 4-alkylthiazolidine-4-carboxylic acids represented by the later-shown general formulas (5), (8), and (9) or salts thereof can be widely used as production materials such as for various industrial chemicals, agricultural chemicals, and pharmaceuticals. Thus, these substances are extremely useful in the industry. In addition, these 4-alkylthiazolidine-4-carboxylic acids or salts thereof can easily undergo a ring-opening reaction at their S—C—N site so as to be derivatized to 2-alkylcysteins. Such a 2-alkylcystein is also useful as a material for producing various industrial chemicals, agricultural chemicals, and pharmaceuticals. However, since the 2-alkylcystein has plural functional groups with high reactivity such as a mercapto group and amino group, it cannot be used as a substrate for carrying out a reaction for yielding a desired derivative selectively. In contrast, the 4-alkylthiazolidine-4-carboxylic acid or a salt thereof can be led to a 2-alkylcysteine derivative of interest by effecting a reaction for obtaining a derivative of a target substance followed by the ring-opening reaction. Thus, the 4-alkylthiazolidine-4-carboxylic acid or a salt thereof is a substance that is important also as a 2-alkylcysteine equivalent.
Although the 4-alkylthiazolidine-4-carboxylic acid or a salt thereof is a compound extremely useful as a reaction material for organic synthesis as stated above, a production process thereof has not yet been known. On the other hand, 5,5-dimethylthiazolidine-4-carboxylic acid has previously been known as a derivative of the 4-alkylthiazolidine-4-carboxylic acid (see Non-Patent Document 2, for example). However, it has a thiazolidine ring which is too rigid to open the ring and return it to a penicillamine derivative. There has also been known an ester or the like of the 4-alkylthiazolidine-4-carboxylic acid, in which nitrogen on the thiazolidine ring is protected by a formyl group (see Patent Document 1 and Non-Patent Document 1, for example). However, since the thiazolidine ring is opened at the same time as deformylation, it is impossible to obtain the 4-alkylthiazolidine-4-carboxylic acids represented by the later-shown general formulas (5), (8), and (9) or the salts thereof in this process.
Patent Document 1: U.S. Pat. No. 6,403,830
Patent Document 2: Japanese Patent Laid-Open No. 2003-201284
Patent Document 3: EP Patent No. 1302467
Non-Patent Document 1: Gerald Pattenden, Stephen M. Thom and Martin F. Jones, Tetrahedron, Vol. 49, No. 10, pp. 2131-2138, 1993
Non-Patent Document 2: Justus Liebigs Ann. Chem. (1966), 697, 140-157